Warnock G L, Kneteman N M, Ryan E A, Rabinovitch A, Rajotte R V
Department of Surgery, University of Alberta, Edmonton, Canada.
Diabetologia. 1992 Jan;35(1):89-95. doi: 10.1007/BF00400857.
Purified human islets and a kidney from the same donor were transplanted into four patients with Type 1 (insulin-dependent) diabetes mellitus. Two of the patients received additional islets that were isolated from multiple donors, cryopreserved, and stored in a tissue bank. The islets were embolized into the liver via the portal vein. Immunosuppression was induced with antilymphocyte globulin and maintained with azathioprine, prednisone and cyclosporine. In the first two patients, fasting serum C-peptide rose to levels of 0.5-2.0 ng/ml during the first 4-8 weeks and mixed meal feeding elicited increases to 2-3 ng/ml. C-peptide secretion persisted for 8 months, but at progressively lower levels and insulin therapy could not be withdrawn. In the next two patients who received cryopreserved islets in addition to fresh islets, serum C-peptide levels (fasting/post-meal) rose to 4-7 ng/ml and serum glucose was more stable, allowing withdrawal of insulin therapy after 69 days in one patient, and reduced insulin doses in the other. The insulin-independent patient has maintained normal fasting glucose, glycosylated haemoglobin, and oral glucose tolerance at 1 year following cessation of daily insulin therapy. Episodes of renal graft rejection occurred in three patients, including the insulin-independent patient. High-dose steroid therapy reversed the rejection in all instances, with apparent preservation of C-peptide secretion. These data show that transplantation of purified freshly-prepared and cryopreserved islets into Type 1 diabetic patients results in prolonged insulin secretion, and that sufficient function could be provided in one patient to sustain euglycaemia in the absence of insulin therapy at 1 year of follow-up.
将来自同一供体的纯化人胰岛和一个肾脏移植到4例1型（胰岛素依赖型）糖尿病患者体内。其中2例患者接受了从多个供体分离、冷冻保存并储存在组织库中的额外胰岛。这些胰岛通过门静脉栓塞到肝脏。使用抗淋巴细胞球蛋白诱导免疫抑制，并使用硫唑嘌呤、泼尼松和环孢素维持。在前2例患者中，空腹血清C肽在最初4 - 8周内升至0.5 - 2.0 ng/ml水平，混合餐进食后升至2 - 3 ng/ml。C肽分泌持续了8个月，但水平逐渐降低，胰岛素治疗无法停用。在另外2例除新鲜胰岛外还接受冷冻保存胰岛的患者中，血清C肽水平（空腹/餐后）升至4 - 7 ng/ml，血糖更稳定，其中1例患者在69天后停用胰岛素治疗，另1例患者胰岛素剂量减少。这位不依赖胰岛素的患者在停止每日胰岛素治疗1年后，空腹血糖、糖化血红蛋白和口服葡萄糖耐量维持正常。3例患者发生了肾移植排斥反应，包括这位不依赖胰岛素的患者。高剂量类固醇治疗在所有情况下都逆转了排斥反应，C肽分泌明显得以保留。这些数据表明，将纯化的新鲜制备和冷冻保存的胰岛移植到1型糖尿病患者体内可导致胰岛素分泌延长，并且在1年的随访中，1例患者获得了足够的功能，在无胰岛素治疗的情况下维持了正常血糖。
